We propose a California wide population-based study to identify the heritable factors predisposing predispose infants to developing bronchopulmonary dysplasia (BPD), a severe disorder of the pulmonary and cardiovascular systems in very low birthweight (VLBW) infants. This will be the first Genome Wide Association Study (GWAS) study of BPD, and will not only have a widespread impact on health care and health delivery for all age groups but it will also enable future studies of diseases involving other organ systems. This study should identify heritable factor(s) and suggest key pathophysiologic pathways responsible for this disorder and thus lead to clinical trials to prevent or modify the course of the disease. Given that children and adolescents with BPD have a permanent impairment of lung function, they are likely predisposed to the early onset of adult chronic obstructive pulmonary disease and pulmonary hypertension. The proposed population based GWAS - BPD incidence study will provide an excellent demonstration project for future and broader proposals investigating the genetic influences on other important childhood or adult disorders and provide valuable resources to all the Institutes of the NIH and the public. Because Stanford hosts the State's comprehensive database on neonatal care and outcomes California Perinatal Quality Care Collaborative (CPQCC), we can link genetic, biomarker, clinical care and outcomes data on virtually all ill newborns in California. This rich resource of biologic and clinical data has yet to be systematically linked to identify how the genome influences the likelihood of BPD or other neonatal or chronic conditions that afflict VLBW infants. Understanding the genetic predisposition of VLBW infants to BPD will yield novel insights into the fundamental mechanisms causing this life-long chronic lung disease and provide new opportunities for preventative and therapeutic strategies. PUBLIC HEALTH RELEVANCE: This population-based study of California infants will identify heritable factors predisposing to BPD, a severe disorder of the pulmonary and cardiovascular systems that results in life long problems, and provide a "proof of principle" that existing clinical databases and biologic samples permit research into genetic and environmental factors leading to diseases that have their origins during fetal and perinatal life.